BACKGROUND Pregnant women infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are more likely to experience preterm birth and their neonates are more likely to be stillborn or admitted to a neonatal unit. The World Health Organization declared in May 2023 an end to the coronavirus disease 2019 (COVID-19) pandemic as a global health emergency. However, pregnant women are still becoming infected with SARS-CoV-2 and there is limited information available regarding the effect of SARS-CoV-2 infection in early pregnancy on pregnancy outcomes. OBJECTIVE AND RATIONALE We conducted this systematic review to determine the prevalence of early pregnancy loss in women with SARS-Cov-2 infection and compare the risk to pregnant women without SARS-CoV-2 infection. SEARCH METHODS Our systematic review is based on a prospectively registered protocol. The search of PregCov19 consortium was supplemented with an extra electronic search specifically on pregnancy loss in pregnant women infected with SARS-CoV-2 up to 10 March 2023 in PubMed, Google Scholar, and LitCovid. We included retrospective and prospective studies of pregnant women with SARS-CoV-2 infection, provided that they contained information on pregnancy losses in the first and/or second trimester. Primary outcome was miscarriage defined as a pregnancy loss before 20 weeks of gestation, however, studies that reported loss up to 22 or 24 weeks were also included. Additionally, we report on studies that defined the pregnancy loss to occur at the first and/or second trimester of pregnancy without specifying gestational age, and for second trimester miscarriage only when the study presented stillbirths and/or foetal losses separately from miscarriages. Data were stratified into first and second trimester. Secondary outcomes were ectopic pregnancy (any extra-uterine pregnancy), and termination of pregnancy. At least three researchers independently extracted the data and assessed study quality. We calculated odds ratios (OR) and risk differences (RDs) with corresponding 95% CI and pooled the data using random effects meta-analysis. To estimate risk prevalence, we performed meta-analysis on proportions. Heterogeneity was assessed by I2. OUTCOMES We included 120 studies comprising a total of 168 444 pregnant women with SARS-CoV-2 infection; of which 18 233 women were in their first or second trimester of pregnancy. Evidence level was considered to be of low to moderate certainty, mostly owing to selection bias. We did not find evidence of an association between SARS-CoV-2 infection and miscarriage (OR 1.10, 95% CI 0.81-1.48; I2 = 0.0%; RD 0.0012, 95% CI -0.0103 to 0.0127; I2 = 0%; 9 studies, 4439 women). Miscarriage occurred in 9.9% (95% CI 6.2-14.0%; I2 = 68%; 46 studies, 1797 women) of the women with SARS CoV-2 infection in their first trimester and in 1.2% (95% CI 0.3-2.4%; I2 = 34%; 33 studies; 3159 women) in the second trimester. The proportion of ectopic pregnancies in women with SARS-CoV-2 infection was 1.4% (95% CI 0.02-4.2%; I2 = 66%; 14 studies, 950 women). Termination of pregnancy occurred in 0.6% of the women (95% CI 0.01-1.6%; I2 = 79%; 39 studies; 1166 women). WIDER IMPLICATIONS Our study found no indication that SARS-CoV-2 infection in the first or second trimester increases the risk of miscarriages. To provide better risk estimates, well-designed studies are needed that include pregnant women with and without SARS-CoV-2 infection at conception and early pregnancy and consider the association of clinical manifestation and severity of SARS-CoV-2 infection with pregnancy loss, as well as potential confounding factors such as previous pregnancy loss. For clinical practice, pregnant women should still be advised to take precautions to avoid risk of SARS-CoV-2 exposure and receive SARS-CoV-2 vaccination.

中文翻译：

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孕妇中的 COVID-19：对流产风险和患病率的系统回顾和荟萃分析。


背景 感染严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 的孕妇更有可能出现早产，其新生儿更有可能死产或入住新​​生儿病房。世界卫生组织于 2023 年 5 月宣布 2019 年冠状病毒病 (COVID-19) 大流行结束，成为全球卫生紧急事件。然而，孕妇仍然感染 SARS-CoV-2，并且关于妊娠早期 SARS-CoV-2 感染对妊娠结局的影响的信息有限。目的和理由我们进行了这项系统评价，以确定感染 SARS-Cov-2 的女性早期妊娠流产的发生率，并比较未感染 SARS-CoV-2 的孕妇的风险。搜索方法 我们的系统评价基于前瞻性注册方案。 PregCov19 联盟的搜索还补充了一项额外的电子搜索，专门针对截至 2023 年 3 月 10 日在 PubMed、Google Scholar 和 LitCovid 中感染 SARS-CoV-2 的孕妇的妊娠丢失情况。我们纳入了对感染 SARS-CoV-2 的孕妇的回顾性和前瞻性研究，前提是它们包含有关妊娠早期和/或中期流产的信息。主要结局是流产，定义为妊娠 20 周之前流产，但也包括报告妊娠 22 或 24 周以内流产的研究。此外，我们报告了一些研究，这些研究定义了妊娠早期和/或中期妊娠发生的流产，但没有具体说明胎龄，并且仅当研究将死产和/或胎儿流产与流产分开时才定义为中期妊娠流产。数据分为妊娠早期和中期。 次要结局是宫外孕（任何宫外妊娠）和终止妊娠。至少三名研究人员独立提取数据并评估研究质量。我们计算了比值比 (OR) 和风险差 (RD) 以及相应的 95% CI，并使用随机效应荟萃分析汇总数据。为了估计风险发生率，我们对比例进行了荟萃分析。通过 I2 评估异质性。结果 我们纳入了 120 项研究，总共涉及 168 444 名感染 SARS-CoV-2 的孕妇；其中 18 233 名妇女处于妊娠早期或中期。证据水平被认为具有低到中等的确定性，主要是由于选择偏差。我们没有发现 SARS-CoV-2 感染与流产之间存在关联的证据（OR 1.10，95% CI 0.81-1.48；I2 = 0.0%；RD 0.0012，95% CI -0.0103 至 0.0127；I2 = 0%；9研究，4439 名女性）。 9.9%（95% CI 6.2-14.0%；I2 = 68%；46 项研究，1797 名女性）感染 SARS CoV-2 的女性在妊娠早期发生流产，流产率为 1.2%（95% CI 0.3-2.4%） ; I2 = 34%；33 项研究；3159 名女性）在妊娠中期。感染 SARS-CoV-2 的女性中异位妊娠的比例为 1.4%（95% CI 0.02-4.2%；I2 = 66%；14 项研究，950 名女性）。 0.6% 的女性终止妊娠（95% CI 0.01-1.6%；I2 = 79%；39 项研究；1166 名女性）。更广泛的影响 我们的研究没有发现任何迹象表明妊娠早期或中期的 SARS-CoV-2 感染会增加流产风险。 为了提供更好的风险评估，需要精心设计的研究，包括受孕和妊娠早期感染或未感染 SARS-CoV-2 的孕妇，并考虑 SARS-CoV-2 感染的临床表现和严重程度与流产的关系，以及潜在的混杂因素，例如之前流产。在临床实践中，仍应建议孕妇采取预防措施以避免接触 SARS-CoV-2 的风险并接受 SARS-CoV-2 疫苗接种。